The regulation of the p53/MDM2 feedback loop by microRNAs
- PMID: 25995995
- PMCID: PMC4435570
- DOI: 10.14800/rd.502
The regulation of the p53/MDM2 feedback loop by microRNAs
Abstract
Tumor suppressor p53 and its signaling pathway play a central role in tumor prevention. The E3 ubiquitin ligase MDM2, which is a direct p53 transcriptional target and also the most critical negative regulator of p53, forms an autoregulatory negative feedback loop with p53 in the cell to tightly regulate the levels and activity of p53. MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that play a critical role in the post-translational regulation of gene expression. Recent studies have revealed that miRNAs directly regulate the levels of p53 or MDM2 to modulate the p53 function in tumor suppression. Recently, we identified miR-339-5p as a new miRNA that directly represses MDM2 to activate p53 and enhance p53 function in tumor suppression. Thus, miRNAs have become a new but important component of the p53 signaling pathway through regulating the p53/MDM2 feedback loop.
Keywords: MDM2; microRNA; p53; tumor.
References
-
- Vousden KH, Prives C. Blinded by the Light: The Growing Complexity of p53. Cell. 2009;137:413–431. - PubMed
-
- Levine AJ, Hu W, Feng Z. The P53 pathway: what questions remain to be explored? Cell Death Differ. 2006;13:1027–1036. - PubMed
-
- Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature. 1992;358:80–83. - PubMed
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous